Benson R T, McDonnell S M, Knowles H J, Rees J L, Carr A J, Hulley P A
Nuffield Department of Orthopaedics, Musculoskeletal Science, Botnar Research Centre, University of Oxford Institute of Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7LD, UK.
J Bone Joint Surg Br. 2010 Mar;92(3):448-53. doi: 10.1302/0301-620X.92B3.23074.
The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff. We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1alpha (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1alpha regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis). The HIF-1alpha expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears. These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.
本研究的目的是调查肩袖肌腱病和撕裂不同阶段组织缺氧和细胞凋亡的发生情况。我们研究了24例患者的组织,这些患者处于撞击(轻度、中度和重度)或肩袖撕裂(部分、小、中、大及巨大)的八个分级阶段,以及三个对照组。使用三种免疫组织化学技术对活检组织进行分析,即针对缺氧诱导因子-1α(一种在缺氧环境中产生的转录因子)、BNip3(一种受缺氧诱导因子-1α调控的促凋亡蛋白)的抗体以及TUNEL(检测凋亡中的DNA片段化)。缺氧诱导因子-1α在轻度撞击以及部分、小、中、大撕裂中表达最高。BNip3在部分、小、中、大撕裂中表达显著增加,但在巨大撕裂中降低。细胞凋亡在小、中、大及巨大撕裂中增加,但在部分撕裂中未增加。这些发现揭示了肩袖整个病理范围内缺氧损伤的证据,这可能导致细胞通过凋亡而丢失。这为肩袖退变的原因提供了新的见解,并突出了可能的治疗选择。